Singh Vimal Kishor, Kumar Neeraj, Kalsan Manisha, Saini Abhishek, Chandra Ramesh
J Stem Cells. 2015;10(1):43-62.
Induced Pluripotent Stem Cells (iPSCs) are self renewable and can differentiate to different types of adult cells, which has shown great promises in the field of regenerative medicine. iPSCs are reprogrammed from human somatic cells through ectopic expression of various transcription factors viz. Oct4, Sox2, Klf4, and c-Myc (OSKM). This novel technology enables derivation of patient specific cells, which possess a potential cure for many diseases. During the last decade, significant progresses have been achieved in enhancing the reprogramming efficiency, safety of iPSCs derivation, development of different delivery techniques by various research groups. Nevertheless, it is important to resolve and define the mechanism underlying the pluripotent stem cells. Major bottleneck which arises during iPSCs generation is the availability of source material (cells/tissues), difficulty to deliver transcription factors with no aberrant genetic modifications and limited reprogramming efficiency. Reprogramming may be achieved by employing different cocktails with number of different transcription factors, application of miRNA and some small molecules such as (Valproic acid, CHiR99021, Sodium butyrate, Vitamin C, Parnate etc). Similarly, various starting source materials have been demonstrated for iPSC based therapies including fibroblasts, cord blood, peripheral blood, keritinocytes, urine, etc., with their specific uses and limitations. Moreover, with the advent of many new reprogramming techniques, various direct delivery methods have been introduced such as using synthetic mRNA expressing pluripotent gene network has been shown to be an appropriate technique to deliver transcription factors and a dozen of small molecules which can replace transcription factors or enhance reprogramming efficiency. This article addresses the iPSCs technology mechanisms, progresses and current perspectives in the field.
诱导多能干细胞(iPSC)具有自我更新能力,能够分化为不同类型的成体细胞,这在再生医学领域展现出了巨大的前景。iPSC是通过异位表达多种转录因子,即Oct4、Sox2、Klf4和c-Myc(OSKM),由人类体细胞重编程而来。这项新技术能够产生患者特异性细胞,对许多疾病具有潜在的治疗作用。在过去十年中,各个研究团队在提高重编程效率、iPSC衍生的安全性以及开发不同的递送技术方面都取得了显著进展。然而,解析和明确多能干细胞的潜在机制仍然很重要。iPSC生成过程中出现的主要瓶颈包括源材料(细胞/组织)的可用性、难以在无异常基因修饰的情况下递送转录因子以及重编程效率有限。可以通过使用含有多种不同转录因子的不同组合、应用miRNA以及一些小分子(如丙戊酸、CHiR99021、丁酸钠、维生素C、反苯环丙胺等)来实现重编程。同样,已证明多种起始源材料可用于基于iPSC的治疗,包括成纤维细胞、脐带血、外周血、角质形成细胞、尿液等,它们各有特定用途和局限性。此外,随着许多新的重编程技术的出现,引入了各种直接递送方法,例如使用表达多能基因网络的合成mRNA已被证明是一种递送转录因子的合适技术,还有一些小分子可以替代转录因子或提高重编程效率。本文探讨了iPSC技术的机制、进展以及该领域的当前观点。